Miniaturized particle manipulation systems may be used for many flow cytometry detection applications, including sensing radioactive particles, nerve agents, organics and explosives, chemical warfare agents, and biological substances. See J. A. Rust et al., Spectrochimica Acta B 61, 225 (2006); F. Arduini et al., Analytical Bioanalytical Chemistry 388, 1049 (2007); S. K. Sharma at al., Spectrochimica Acta Part A 61, 2404 (2005); P. R. Lewis at al. IEEE Sensors Journal 6, 784 (2006); and T. M. Chinowsky et al., Biosensors and Bioelectronics 22, 2268 (2007).
In addition, Bromage et al. developed a portable confocal microscope capable of high-resolution microscopy for numerous detection applications. See T. G. Bromage et al., 2003, In A. Mendez-Vilas (Ed.), Science, technology, and education of microscopy: an overview. Formatex: Badajoz. pp. 742-752. These field-deployable biodetection systems would also be useful in screening infectious disease and bioterrorism threats in industrial environments such as food and beverage processing facilities. See L. M. Wein and Y. Liu. PNAS 102, 9984 (2005). However, many of the current systems suffer from the inability to (1) detect trace quantities of substances, and (2) handle complex raw samples. In this regard, advances in sample preparation technology are crucial for the development of robust detector systems that are field-deployable.
Dielectrophoresis (DEP) has been utilized by numerous labs to focus particles in microfluidic systems; however, these systems typically generate single streams of focused particles similar to commercial sheath-flow flow cytometers. See H. Morgan, at al., Proceedings of the IEEE Nanobiotechnology 150 (2) (2003) 76-81; C. Lin, at al., Journal of Microelectromechanical Systems 13 (6) (2004) 923-932; C. Yu et al., Journal of Microelectromechanical Systems 14 (3) (2005) 480-487; and D. Holmes et al., Biosensors and Bioelectronics 21 (8) (2006) 1621-1630. Morgan et al. utilized two closely spaced (10 μm) electrode chips to provide 3D focusing of particles, but it is difficult to generate single-file streams of particles with the device. See H. Morgan, et al., Proceedings of the IEEE Nanobiotechnology 150 (2) (2003) 76-81. Holmes et al. generated single-file particle focusing a similar system configuration, but the chip format used in this design still produces only one stream of focused particles. See D. Holmes et al., Biosensors and Bioelectronics 21 (8) (2006) 1621-1630.
Meanwhile, magnetic forces have been utilized extensively for their high selectivity and ease of use in sample preparation. See M. A. M. Gijs, Microfluidics Nanofluidics 1, 22 (2004). Target analytes can be bound to magnetic particles through designed surface chemistries, enabling highly selective forces to be applied only to these analytes due to the fact that most substances are transparent to magnetic fields. See N. Pamme and C. Wilhelm, Lab on a Chip 6, 974 (2006). This is particularly important for handling complex sample matrices containing substances that can interfere with downstream analysis techniques.
Labs are developing immunomagnetic sample preparation methods for detection systems. See M. R. Blake and B. C. Weimer, Applied and Environmental Microbiology 63, 1643 (1997); T. M. Straub et al., Journal of Microbiology Methods 62 (3) (2005) 303-316; and H. Gu et al., Chemical Communications 9 (2006) 941-949. Chandler et al. demonstrated an automated system for detecting bacteria in animal carcasses using PCR and DNA microarrays. See D. P. Chandler et al., International Journal of Food Microbiology 70 (1) (2001) 143-154. The system developed by Chandler et al. utilizes an electromagnet and a ferromagnetic porous material for generating large magnetic field gradients to trap magnetic particle chaperones bound to target analytes. Mulvaney et al. utilized a similar scheme, but with a giant magnetoresistance sensor for detection. See S. P. Mulvaney et al., Biosensors and Bioelectronics 23 (2) (2007) 191-200.
However, non-optical detection schemes such as surface plasmon resonance and electrochemical detection often suffer from lower sensitivity and higher background noise, while more sensitive techniques such as PCR and microarrays have slower throughput, are susceptible to contamination, and are difficult to scale-down and integrate. See T. M. Chinowsky et al., Biosensors and Bioelectronics 22 (9-10) (2007) 2268-2275; and F. Arduini et al., Analytical Bioanalytical Chemistry 388, 1049 (2007). Recent work in microfluidic ELISA systems have shown both high sensitivity and rapid processing time; however, the reagents used in these systems require physical isolation prior to the interrogation step, a requirement that significantly increases device complexity. See M. Hermann et al., Lab on a Chip 6 (2006) 555-560; and M. Herrmann et al., Lab on a Chip 7 (2007) 1546-1552.